Full Text HL-92-07
COLLABORATIVE PROJECTS ON WOMEN'S HEALTH
NIH GUIDE, Volume 21, Number 13, April 3, 1992
RFA: HL-92-07
P.T. 34, II
Keywords:
Cardiovascular Diseases
Pulmonary Diseases
Biomedical Research, Multidiscipl
Human Reproduction/Fertility
Physiology, Human
National Heart, Lung, and Blood Institute
Letter of Intent Receipt Date: November 13, 1992
Application Receipt Date: December 9, 1992
PURPOSE
The National Heart, Lung, and Blood Institute (NHLBI) invites the
concurrent submission of small groups of scientifically related
research project applications related to women's health issues. The
goal of this program is to foster collaborative research in currently
underinvestigated areas of women's health that relate to
cardiovascular, lung, and blood diseases.
The special feature of this program is the concurrent submission of
research project grant applications by investigators who wish to
collaborate on a common theme, but do not require extensive shared
physical resources or core functions to conduct the research. In order
to be responsive to this Request for Application (RFA), a minimum of
three independent investigators with related research objectives may
submit concurrent, collaborative, cross-referenced individual research
project grant applications that address a common theme. The common
theme may be one that spans the traditional boundaries of
cardiovascular, lung, and blood research (e.g., thromboembolic events)
or it may deal with a single disease or condition from several points
of view (e.g., prevention, diagnosis, and treatment of chest pain).
Investigators may submit applications for basic science and small
clinical studies including biobehavioral and prevention research.
Investigators are encouraged to propose studies that focus on both
normal development and disease in various phases in women. Many
studies demonstrate gender differences; this solicitation encourages
research that compares women with women--of different ages, lifestyles,
racial/ethnic groups, and socioeconomic status--to understand clinical
attributes of normal and diseased conditions within the gender.
HEALTHY PEOPLE 2000
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priorities. This RFA,
Collaborative Projects on Women's Health, addresses several priority
areas including heart disease and stroke, physical activity and
fitness, and nutrition, as they relate to cardiovascular, lung, and
blood diseases. Potential applicants may obtain a copy of "Healthy
People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy
People 2000" (Summary Report: Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington, DC
20402-9325 (telephone 202/783-3238).
ELIGIBILITY REQUIREMENTS
Domestic public and private, for-profit and non-profit institutions and
organizations are eligible to apply in response to this RFA.
Applications from women and minority investigators and institutions are
encouraged. Awards will not be made to foreign institutions.
MECHANISM OF SUPPORT
The support mechanism for this program will be the traditional
individual research project grant (R01). Applicants will plan and
execute the research programs and are requested to furnish their own
estimates of the time required to achieve the objectives of the
proposed research project. Up to five years of support may be
requested. At the end of the official award period, renewal
applications may be submitted for peer review and competition for
support through the unsolicited grant process of the NIH. It is
anticipated that support for the present program will begin in July
1993. Administrative adjustments in project period and/or amount of
support may be required at the time of the award.
All current policies and requirements that govern the research grant
programs of the NIH will apply to grants awarded in connection with
this RFA.
Since a variety of approaches would represent valid responses to this
announcement, a range of costs is expected among individual grants
awarded. However, a collaborative group of R01s may not exceed
$1,000,000 total requested costs (direct and indirect) each year, and
the average total requested cost of applications within a group may not
exceed the average total cost of NHLBI R01 grants ($220,000). Any
equipment requested must be especially justified. Requests for
expensive pieces of equipment are not encouraged. Collaborative
arrangements involving other institutions must be strongly justified
and should be discussed with program staff prior to submission of the
applications.
Individual investigators may request a small amount of funds, not to
exceed 15 percent of direct costs for the time and effort contributed
toward coordination of overall research and for that proportion of
shared resources that is necessary for the research.
FUNDS AVAILABLE
Although the financial plans for fiscal year 1993 include $5,000,000
for the total costs of this program, award of grants pursuant to this
RFA is contingent upon receipt of funds for this purpose. It is
anticipated that up to six collaborative groups (15-25 R01 awards) will
be supported under this program. The number and specific amount to be
awarded will depend on the merit and scope of the applications received
and on the availability of funds.
RESEARCH OBJECTIVES
Background
The development and progression of cardiovascular, lung, and blood
diseases in women represent areas of significant opportunity for
research that may lead to improved strategies for prevention,
diagnosis, and treatment. Cardiovascular diseases are the leading
cause of death in women in the United States. A number of problems in
clinical cardiology would benefit immediately from improved
understanding of how gender affects the cardiovascular system. For
example, chest pain in women presents a major diagnostic and
therapeutic challenge. Although angiographic studies demonstrate that
women have a lower prevalence of coronary artery disease, anginal type
chest pain is more common in women. The low prevalence of coronary
disease at certain ages renders currently available noninvasive
diagnostic methods ineffective in many symptomatic women. The
diagnosis of angina pectoris in women may be complicated by a higher
prevalence of conditions associated with chest pain that, generally,
have a favorable prognosis, such as mitral valve prolapse, variant
angina, and microvascular angina. Nevertheless, women may suffer
higher case fatality rates for myocardial infarction and have increased
incidence of postinfarction angina and heart failure, despite a higher
resting ejection fraction. It has been reported that women undergoing
surgical revascularization have higher perioperative mortality and less
favorable functional improvement, despite better left ventricular
function and less apparent anatomic disease. Although recent studies
suggest gender differences in the application of coronary artery
catheterization and coronary artery bypass surgery, it may be difficult
to dissociate age, comorbidity, and gender. Whether differential
utilization by gender represents overuse in men, underuse in women, or
appropriate use, and the extent to which this affects treatment and
outcome are unknown.
Several research groups have demonstrated gender differences in
vascular reactivity. Coronary artery blood flow and its response to
stress or exertion may underlie variations in the perception of chest
pain and clinical manifestations of coronary heart disease (CHD), but
this area has been largely unexplored. There is growing evidence that
biologic differences identified between the genders may modulate the
effect of standard risk factors for CHD. Sex hormone receptors have
been identified in human coronary arteries, but their significance is
unclear. In addition, although previous studies have shown that stress
affects the levels of reproductive and other hormones, the relationship
of stress to the mechanisms involved in atherogenesis in women is still
largely unknown.
Persons who engage in regular physical activity exhibit significantly
lower rates of coronary heart disease and stroke, as well as lower
prevalence of coronary risk factors such as glucose intolerance,
hypertension, and low HDL cholesterol levels. The physiological
synergy among the triad of smoking cessation, weight control, and
physical activity appears to be particularly relevant for women, yet
this area has been explored inadequately. Little is known about the
specific personal, social, and environmental barriers to increased
activity that are present at various life stages, or about methods for
tailoring interventions to women of different ages, health status, and
backgrounds.
Chronic airways disease, which includes asthma and chronic obstructive
pulmonary disease (COPD), is the most prevalent lung problem in the
United States today, but its particular effects in women have received
little attention. Asthma in pregnancy has been associated with an
increased risk of gestational hypertension, preeclampsia, and
significant excesses of preterm births, low birth weights, neonatal
hypoxia, and neonatal mortality, yet the underlying mechanisms are
poorly understood. Research on older asthmatic women indicates that
steroid therapy is associated with a high risk for increased rate of
bone loss, but the long-term risks and benefits of this treatment are
unknown. COPD is largely a smoking-related disorder. Women smokers
with early signs of COPD have been found to exhibit substantially
higher airways reactivity than men. The reasons why women also have
relatively more difficulty quitting smoking, and gain more weight when
they do quit, remain unknown.
In the area of blood diseases, there are many unexplored questions
about thrombotic and antithrombotic processes that take place during
various phases of a woman's life, including puberty, menopause, and
pregnancy. Clinical decisions about anticoagulant and fibrinolytic
therapy for women would benefit from more accurate information about
gender-related differences in response to these therapies. Important
questions exist concerning such topics as anticoagulation following
surgery to prevent deep venous thrombosis and pulmonary embolism,
anticoagulation during pregnancy, and fibrinolytic therapy for older
women. Further research is also needed on thrombosis and hemostasis in
specific subpopulations of women, such as those with sickle cell
disease or systemic lupus erythematosus.
The hematopoietic microenvironment influences growth and
differentiation of hematopoietic cells. Several aspects of the
hematopoietic process are prime targets for questions pertaining to the
influence of gender and possible regulation by sex and other hormones.
Newer evidence suggests that the marrow is intimately related to bone,
its surrounding tissue, and that bone formation may influence marrow
development. Thus, the elucidation of the interrelationships among sex
hormones, bone, and marrow may provide insight into the process of
blood cell formation, bone development and maintenance, and
osteoporosis.
Examples of Research Areas
Examples of research that would be responsive to this RFA are given
below. These research topics are intended to provide a perspective on
the scope of research that would meet the purpose of this program. It
is not required that all or any of them be included in a particular
group of applications. Investigators are encouraged to consider other
topics relevant to this program.
o Assessment of myocardial perfusion and metabolism in women with the
goal of distinguishing, among women with ischemia-like chest pain,
those in whom symptoms are an early manifestation of myocardial
ischemia.
o Determination of the location and concentration of vascular hormone
receptors in women and/or female animal models and evaluation of
receptor-mediated changes in vasomotor tone
o Elucidation of the mechanisms that mediate the effects of stress on
lipid metabolism and atherogenesis, such as the relationship between
stress, ovarian dysfunction, and premenopausal myocardial infarction.
o Development and evaluation of interventions to promote physical
activity to enhance cardiovascular and pulmonary fitness among adult
women at various life stages, such as entry into the work force,
parenthood, and retirement.
o Evaluation of the effect of asthma and its treatment on pregnant
women, the developing fetus, and perinatal outcome; examination of the
benefits and risks of steroid therapy for asthma in postmenopausal
women who have been treated with steroids for various lengths of time.
o Investigation of mechanisms that contribute to increased airways
responsiveness in women; studies of synergistic effects of airways
reactivity, cigarette smoking, and environmental/occupational exposures
in women.
o Determination of whether or not aspects of nicotine dependence
affect smoking cessation rates in women and whether or not age, life
stage, physical activity, and marital, health, racial/ethnic, and
socioeconomic status differentially affect cessation rates.
o Elucidation and exploration of reproductive problems in women with
sickle cell disease (SCD), e.g., specific cause of menarchial delay,
effect of SCD on conception and pregnancy outcome.
o Investigation of thromboembolic events as a function of a woman's
normal development and of life stages such as pregnancy and
postmenopause; determination of factors that influence response to
thrombolytic agents and anticoagulants in women; and development of
safe and effective anticoagulants for use during pregnancy.
o Investigation of the role and effect of sex hormones on the
hematopoietic microenvironment and the subsequent growth and
differentiation of hematopoietic cells
Exclusions
This RFA is intended to support individual research grants. Studies in
men will not be responsive to this RFA. Large population-based
studies, such as epidemiologic surveys and clinical trials, will be
considered unresponsive to this announcement.
SPECIAL REQUIREMENTS
Upon initiation of the program, annual meetings will be held in
Bethesda, Maryland, to encourage an exchange of information and ideas
among investigators who participate in this program.
STUDY POPULATIONS
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF MINORITIES IN RESEARCH STUDY
POPULATIONS
This RFA focuses on women. NIH and ADAMHA policy is that applicants
for research grants are required to include minorities in study
populations so that research findings can benefit all persons at risk
of the disease, disorder, or condition under study. Special emphasis
should be placed on the need for inclusion of minorities in studies of
diseases, disorders, and conditions that disproportionately affect
them. If minorities are excluded or are inadequately represented in
clinical research, a clear, compelling rationale for exclusion for
inadequate representation should be provided.
The composition of a proposed study population must be described in
terms of racial/ethnic group, together with a rationale for its choice.
In addition, racial/ethnic issues should be addressed in developing a
research design and sample size appropriate for the scientific
objectives of the study. Information should be included in the form PHS
398 in Section 2, 1-4 of the research plan AND summarized in Section 2,
5, Human Subjects. Applicants are urged to assess carefully the
feasibility of including the broadest possible representation of
minority groups. However, NIH recognizes that it may not be feasible
or appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority populations
(i.e., Native Americans (including American Indians or Alaskan
Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale
for studies on single minority population groups should be provided.
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, (and
preventive strategies), diagnosis, or treatment of diseases, disorders,
or conditions, including but not limited to clinical trials.
The usual NIH policies concerning research on human subjects also
apply. Basic research or clinical studies in which human tissues cannot
be identified or linked to individuals are excluded. However, every
effort should be made to include human tissues from minorities when it
is important to apply the results of the study broadly, and this should
be addressed by applicants. If the application does not contain the
required information, it will be returned.
Peer reviewers will address specifically whether the research plan in
the application conforms to these policies. If the representation of
minorities is inadequate to answer the scientific question(s) addressed
AND the justification for the selected study population is inadequate,
it will be considered a scientific weakness or deficiency in the study
design and will be reflected in assigning the priority score to the
application.
All applications for clinical research submitted to NIH are required to
address these policies. NIH funding components will not award grants
or cooperative agreements that do not comply with these policies.
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that
includes identification of other participating investigators and any
other institutions, and a descriptive title. The NHLBI requests such
letters only for the purpose of providing an indication of the number
and scope of applications to be received and, therefore, usually does
not acknowledge their receipt. A letter of intent is not binding, and
it will not enter into the review of any application subsequently
submitted, nor is it a necessary requirement for application. This
letter of intent is to be received no later than November 13, 1992, and
is to be sent to:
Dr. Charles Turbyfill
Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 553
Bethesda, MD 20892
APPLICATION PROCEDURES
The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants. This form is available in the applicant
institution's office of sponsored research or business office. It may
also be obtained from the Office of Grants Inquiries, National
Institutes of Health, Room 449, Westwood Building, Bethesda, MD 20892.
In preparing the application, it is important that the points
identified in the section on REVIEW CONSIDERATIONS in this announcement
are addressed. The new page limitation requirements must be observed.
However, an additional two pages will be allowed to describe the
collaborative arrangements in terms of the science and mechanisms for
collaboration. Applicants should contact one of the program
administrators listed under INQUIRIES to seek clarification or discuss
any questions related to this announcement.
To identify the application as a response to this RFA, Check "YES" on
Item 2a of page 1 of the application and enter the title,
"Collaborative Projects on Women's Health" and the RFA number HL-92-07.
THE RFA LABEL ENCLOSED WITH THE PHS 398 FORM MUST BE AFFIXED TO THE
BOTTOM OF THE FACE PAGE OF THE ORIGINAL APPLICATION. FAILURE TO USE
THIS LABEL COULD RESULT IN DELAYED PROCESSING OF THE APPLICATION.
Each group of applications must include a succinct description of the
scientific relationship among the group of R01s; plans for
collaboration, interaction, and communication among investigators in
the group of applications; and the name of the individual responsible
for organizing and maintaining effective collaboration.
In the preparation of the budget for the grant application, applicants
should request travel funds for a two-day meeting each year to be held
in Bethesda, Maryland. Applicants should also include a statement in
the application indicating a willingness to participate in such
meetings.
Send or deliver the completed application and three signed, exact
photocopies in single packages boxed together to the following office,
making sure that the original applications with the RFA label attached
are on top and bound together:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892
SEND AN ADDITIONAL TWO COPIES OF THE APPLICATIONS IN A SINGLE PACKAGE
TO DR. CHARLES L. TURBYFILL AT THE ADDRESS LISTED UNDER LETTER OF
INTENT. IT IS IMPORTANT TO SEND THESE TWO COPIES AT THE SAME TIME AS
THE ORIGINAL AND FOUR COPIES ARE SENT TO THE DIVISION OF RESEARCH
GRANTS. OTHERWISE THE NHLBI CANNOT GUARANTEE THAT THE APPLICATION WILL
BE REVIEWED IN COMPETITION FOR THIS RFA.
Applications must be received by December 9, 1992. An application
received after this date will be returned to the applicant.
REVIEW CONSIDERATIONS
Upon receipt, applications will be reviewed for responsiveness to the
objectives of this RFA. If an application or group of applications is
judged unresponsive, the application(s) will be returned to the
applicant. If an application submitted in response to this RFA is
identical to or substantially the same as one already submitted to the
NIH for review in the same cycle, the principal investigator will be
asked to withdraw the pending application before the new one is
accepted. Simultaneous submission of identical applications will not
be allowed.
Applications judged to be responsive will be reviewed for scientific
and technical merit by an initial review group that will be convened by
the Division of Extramural Affairs, NHLBI, solely to review these
applications.
This initial review will include a triage. The NHLBI will withdraw
from further consideration applications judged to be noncompetitive and
promptly notify the Principal Investigator and the official signing for
the applicant organization. Those applications judged to be
competitive will be further evaluated for scientific and technical
merit by usual peer review procedures. Each application will receive
a priority score based upon review criteria listed below.
Review Criteria: Factors to be considered in the evaluation of each
application will be similar to those used in review of traditional
research project grant applications and, in addition, will include
overall proposed collaboration. Major factors to be considered in the
evaluation of applications will include:
1. Scientific merit of the proposed projects, including innovation,
originality, and feasibility of the approach, and adequacy of the
experimental design;
2. Competence of the investigators to accomplish the proposed research
goals, their commitment, and the time devoted to the program;
3. Integration of the component R01s into an enterprise with a common
theme and adequate plans for collaboration, interaction, and
communication of information among participating investigators;
4. Adequacy of facilities for performance of the proposed research,
including laboratory facilities, proposed instrumentation and, when
needed, data management systems;
5. Appropriateness of the budget for the proposed project.
AWARD CRITERIA
The anticipated date of award is July 1993.
Funding decisions will be made on the basis of scientific and technical
merit as determined by peer review, program needs and balance, and the
availability of funds.
INQUIRIES
Inquiries regarding this request for applications may be directed to
the following program administrators:
Patrice Desvigne-Nickens, M.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
Federal Building, Room 3C06
Bethesda, MD 20892
Telephone: (301) 496-1081
FAX: (301) 480-6282
Carol Vreim, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
Westwood Building, Room 6A16
Bethesda, MD 20892
Telephone: (301) 496-7208
Fax: (301) 496-9886
Carol Letendre, Ph.D.
Division of Blood Diseases and Blood Resources
National Heart, Lung, and Blood Institute
Federal Building, Room 516A
Bethesda, MD 20892
Telephone: (301) 496-8966
Fax: (301) 402-1622
Elaine Stone, Ph.D., M.P.H.
Division of Epidemiology and Clinical Applications
National Heart, Lung, and Blood Institute
Federal Building, Room 604A
Bethesda, MD 20892
Telephone: (301) 496-3503
Fax: (301) 480-1357
For fiscal and administrative matters, contact:
Thomas Turley
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 4A12
Bethesda, MD 20892
Telephone: (301) 496-7255
Fax: (301) 402-1200
AUTHORITY AND REGULATIONS
These programs are described in the Catalog of Federal Domestic
Assistance numbers: 93.837, Heart and Vascular Diseases Research;
93.838, Lung Diseases Research; 93.839, Blood Diseases and Resources
Research. Awards will be made under the authority of the Public Health
Service Act, Section 301 (42 USC 241) and administered under PHS grants
policies and Federal regulations, most specifically 42 CFR Part 52 and
45 CFR Part 74. This program is not subject to the intergovernmental
review requirements of Executive Order 12372, or to Health Systems
Agency review.
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